Plasma Separation by Centrifugation and Subsequent Plasma Filtration: Impact on Survival in a Pig Model of Sepsis

The impact on survival of a combination of plasma separation by centrifugation and subsequent plasma filtration was tested in a bacterial sepsis model in pigs. In this animal study 19 pigs were included. Groups II and III received an intravenous lethal dose of live Staphylococcus aureus over 1 h; group I received saline (non‐septic control—NC). Groups I and II were treated by an extracorporeal circuit consisting of online centrifugation and subsequent plasma filtration (group II: treated group—TG) for 4 h; group III had no specific treatment (septic control, SC). The observation time was 7 days. All animals of group I (NC) and group II (TG) survived, while all animals of group III (SC) died during the observation time. Extracorporeal therapy with online centrifugation and plasma filtration significantly improved survival in a pig model of sepsis. Further studies with this approach are encouraged.     

Circulating myeloid‐derived suppressor cells correlate with clinical outcome in Hodgkin Lymphoma patients treated up‐front with a risk‐adapted strategy

In the attempt to find a peripheral blood biological marker that could mirror the dysregulated microenvironment of Hodgkin Lymphoma (HL), we analysed the amount of myeloid‐derived suppressor cells (MDSC), including the three main sub‐types (monocytic, granulocytic and CD34 + fraction). The absolute MDSC count was investigated in 60 consecutive newly diagnosed HL patients and correlated with clinical variables at diagnosis and outcome. Patients received standard‐of‐care chemotherapy with the exception of interim fluorodeoxyglucose positron emission tomography (PET‐2)‐positive patients, who were switched early to a salvage regimen. All MDSC subsets were increased in HL patients compared to normal subjects (P < 0·0001) and were higher in non‐responders. However, a strong prognostic significance was limited to immature (CD34⁺) MDSC. A cut‐off level of 0·0045 × 10⁹/l for CD34⁺MDSC resulted in 89% (95% confidence interval [CI] 52–99%) sensitivity and 92% (95% CI 81–98%) specificity. The positive predictive value to predict progression‐free survival was 0·90 for PET‐2 and 0·98 for CD34⁺MDSC count; the negative predictive value was 0·57 for PET‐2 and 0·73 for CD34⁺MDSC. PFS was significantly shorter in patients with more than 0·0045 × 10⁹ CD34⁺MDSC cells/l at diagnosis and/or PET‐2 positivity (P < 0·0001). In conclusion, all circulating MDSC subsets are increased in HL; CD34⁺MDSC predict short PFS, similarly to PET‐2 but with the advantage of being available at diagnosis.     

Electrocardiographic diagnosis of atrial infarction in patients with acute inferior ST‐segment elevation myocardial infarction

Background

Patients with atrial myocardial infarction (ATMI) have frequent cardiac and noncardiac complications. However, ATMI is uncommonly diagnosed because of its nonspecific ECG changes. Our objective was to analyze the ECG characteristics of ATMI in patients with inferior STEMI.

Hypothesis

Electrocardiographic P wave parameters can help in diagnosis of ATMI.

Methods

We evaluated 932 patients who underwent coronary angiography and recruited 39 patients with ATMI and 33 patients without ATMI with inferior STEMI for a retrospective study. Twelve‐lead ECGs were obtained to measure P‐wave parameters in diagnosis of ATMI. P‐wave parameters and PR‐segment displacement were compared in patients with and without ATMI.

Results

In inferior leads, PWD and PWDisp were significantly longer in the ATMI group than in the non‐ATMI group (limb lead II, 109.79 ±15.51 ms and 86.65 ±5.02 ms, respectively; P < 0.001; limb lead III, 108.31 ±12.51 ms and 85.27 ±7.47 ms, P < 0.001; aVF, 106.49 ±13.68 ms and 83.01 ±7.89 ms, P < 0.001; PWDisp, 41.67 ±10.72 ms and 25.18 ±5.17 ms, P < 0.001). By contrast, PWA was significantly lower in the ATMI group than in the non‐ATMI group (limb lead II, 0.96 ±0.18 mV and 1.39 ±0.22 mV, respectively; P < 0.001; limb lead III, 0.90 ±0.11 and 1.21 ±0.23, P < 0.001; aVF, 0.88 ±0.17 and 1.26 ±0.28, P < 0.001). PR‐segment displacement was found in 8 (20.5%) patients with ATMI. A PWD ≥95.5 ms in lead DII diagnosed ATMI with a higher sensitivity and specificity (90%, 94%) than did PWA or PWDisp.

Conclusions

This study suggests P‐wave parameters might be considered ECG findings in diagnosis of ATMI in patients with inferior STEMI.     

Dose‐intensified treatment of Burkitt lymphoma and B‐cell lymphoma unclassifiable, (with features intermediate between diffuse large B‐cell lymphoma and Burkitt lymphoma) in young adults (<50 years): A comparison of two adapted BFM protocols

The chemotherapy dose‐intensity in two adapted German BFM paediatric protocols (BFM 90 and NHL 86) was compared in contemporaneously treated adults <50 years with Burkitt lymphoma and B‐cell lymphoma unclassifiable, with features intermediate between diffuse large B‐cell lymphoma and Burkitt lymphoma (collectively referred to as BL). In BFM 90, primary prophylaxis with Granulocyte‐colony‐stimulating factor was used, postinduction treatment was started at granulocytes ≥0.5 × 10⁹/L (≥1.0 × 10⁹/L in NHL 86) with a higher mean methotrexate dose (2.9 g/m²/cycle, n = 23; 1.6 g/m²/cycle in NHL 86, n = 22, P < 0.001). Intervals between consecutive treatment‐cycles were shorter in BFM 90 (P < 0.001) with no additional toxicity. However, the two‐year failure‐free survival with BFM 90 (82%) was similar to that achieved with NHL 86 (72%, P = 0.33). We conclude that BFM 90 enables safe intensification of therapy in young adults with BL compared to NHL 86, but registry‐based studies are required to further evaluate the antineoplastic effects and cost‐effectiveness of the two therapeutic approaches. Am. J. Hematol., 2010. © 2010 Wiley‐Liss, Inc.     

Hodgkin lymphoma post‐transplant lymphoproliferative disorder: A comparative analysis of clinical characteristics,prognosis, and survival

Hodgkin lymphoma post‐transplant lymphoproliferative disorder (HL‐PTLD) is an uncommon PTLD with unclear prognosis and differences between HL‐PTLD and immunocompetent HL are not well defined. Patient characteristics were compared among 192 patients with HL‐PTLD from the Scientific Registry of Transplant Recipients and 13,847 HL patients in SEER (HL‐SEER). Overall survival (OS) and disease‐specific survival (DSS) were compared after exact matching. Additionally, multivariable analyses were used to identify prognostic markers of survival and associations between treatment and survival. Median time from transplant to HL‐PTLD diagnosis was 88 months. When compared with HL‐SEER, patients with HL‐PTLD were older (median age, 52 vs. 36 years, P = 0.001), more likely male (73% vs. 54%, P < 0.001), Caucasian (81% vs. 70%, P = 0.02), and had extranodal disease (42% vs. 3%, P < 0.001). Five‐year OS for patients with HL‐PTLD was 57% versus 80% for HL‐SEER (P < 0.001); DSS was also inferior (P < 0.001). For patients with HL‐PTLD, the use of any chemotherapy was associated with decreased hazard of death (HR = 0.36, P < 0.001). Furthermore, patients who received no chemotherapy or nontraditional HL regimens had increased hazard of death (aHR = 2.94, P = 0.001 and 2.01, P = 0.04) versus HL‐specific chemotherapy regimens. In multivariable analysis, advanced age and elevated creatinine were associated with inferior OS (aHR = 1.26/decade P < 0.001 and 1.64/0.1 mg/dL increase P = 0.02). A prognostic score based on the number of these adverse factors (0, 1, 2) was associated with 10‐year OS rates of 79%, 53%, and 11%, respectively (P < 0.001). Altogether, HL‐PTLD patients have inferior survival when compared with HL‐SEER. Furthermore, treatment with HL‐specific chemotherapy was associated with improved OS, whereas age and creatinine identified patients with markedly divergent survival. Am. J. Hematol. 91:560–565, 2016. © 2016 Wiley Periodicals, Inc.     

Clinico‐pathological study of Hodgkin's lymphoma in a cancer center in Taiwan

The incidence rate of Hodgkin's lymphoma (HL) in Asia is much lower than that of western countries. This study demonstrates the incidence rate and the clinico‐pathological features of HL in a cancer center in Taiwan with respect to demographics, histological subtypes and clinical outcomes. We evaluated the clinical, morphological and immunohistochemical features of 42 patients with HL during the period of 1995–2002. Clinico‐pathological features and follow‐up were scrutinized. There were 21 males and 21 females. The incidence rate of HL in malignant lymphoma in our center was 7%. The median age was 26 years old. There was no apparent bimodal age distribution. The most prevalent histological subtype was nodular sclerosis (69%). Mixed cellularity, lymphocyte rich, lymphocyte depletion, nodular lymphocyte predominance and unclassified was 4.8%, 4.8%, 0%, 7% and 14% respectively. The most common site at presentation was the cervical lymph node (31 cases; 74%). Clinically, 1 (2%) had stage I disease, 23 (55%) stage II, 8 (19%) stage III and 10 (24%) stage IV. Two cases had rare primary bone marrow HL of stage IV. Both cases died within 1 month. Clinical stage (P = 0.09) and age (P < 0.001) were prognostic parameters determining the overall survival.     

Assessment of adrenal function in cirrhotic patients using concentration of serum‐free and salivary cortisol

Objective: Because over 90% of serum cortisol is bound to albumin and corticosteroid‐binding globulin (CBG), changes in these proteins can affect measures of serum total cortisol levels in cirrhotics without altering serum‐free and salivary cortisol concentrations. Methods: We assessed basal (T₀) and post‐synacthen (T₆₀) serum total cortisol, serum‐free and salivary cortisol in 125 consecutive cirrhotics (95 non‐septic and 30 septic patients with a Child>8). Results: Serum total cortisol levels significantly decreased from the Child A–C non‐septic group, as did albumin and CBG levels, with a non‐significant rise in serum‐free cortisol concentrations. Non‐septic patients with low albumin (≤25 g/L) or CBG levels (≤35 mg/L) had lower T₀ serum total cortisol levels than patients with near‐normal albumin (303.4 vs. 382.6 nmol/L; P=0.0035) or with normal CBG levels (289.9 vs. 441.4 nmol/L; P<0.0001), respectively, despite similar serum‐free cortisol or salivary cortisol concentrations. Subnormal T₆₀ serum total cortisol concentrations (<510.4 nmol/L) were measured in 7.2% of all patients (Child C: 14.5% vs. Child A and B: 0%; P=0.0013) but no patients exhibited symptoms suggesting adrenal insufficiency. Patients with or without subnormal T₆₀ total cortisol had similar T₀ salivary cortisol and serum‐free cortisol concentrations. A trend was observed towards high serum‐free cortisol concentrations and mortality in multivariate analysis. Conclusions: Serum total cortisol levels overestimated the prevalence of adrenal dysfunction in cirrhotics with end‐stage liver disease. Since serum‐free cortisol cannot be measured routinely, salivary cortisol testing could represent a useful approach but needs to be standardized.     

No survival benefit associated with routine surveillance imaging for Hodgkin lymphoma in first remission: a Danish‐Swedish population‐based observational study

The use of routine imaging for patients with classical Hodgkin lymphoma (HL) in complete remission (CR) is controversial. In a population‐based study, we examined the post‐remission survival of Danish and Swedish HL patients for whom follow‐up practices were different. Follow‐up in Denmark included routine imaging, usually for a minimum of 2 years, whereas clinical follow‐up without routine imaging was standard in Sweden. A total of 317 Danish and 454 Swedish comparable HL patients aged 18–65 years, diagnosed in the period 2007–2012 and having achieved CR following ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine)/BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) therapy, were included in the study. The cumulative progression rates in the first 2 years were 4% (95% confidence interval [CI] 1–7) for patients with stage I–II disease vs. 12% (95% CI 6–18) for patients with stage III–IV disease. An imaging‐based follow‐up practice was not associated with a better post‐remission survival in general (P = 0·2) or in stage‐specific subgroups (P = 0·5 for I–II and P = 0·4 for III–IV). Age ≥45 years was the only independent adverse prognostic factor for survival. In conclusion, relapse of HL patients with CR is infrequent and systematic use of routine imaging in these patients does not improve post‐remission survival. The present study supports clinical follow‐up without routine imaging, as encouraged by the recent Lugano classification.     

Effect of biotherapeutics on cyclosporin‐induced Clostridium difficile infection in mice

Background and Aim: Immunosuppressive therapy may precipitate Clostridium difficile associated disease (CDAD). We evaluated the role of cyclosporin in the development of CDAD in the experimental mouse model and studied the effect of probiotic and epidermal growth factor (EGF) as biotherapeutics measures. Methods: BALB/c mice (n = 24) were divided into four groups. Group I animals not given any inoculum served as controls. Animals in the remaining three groups (Group II, III and IV) were given cyclosporin daily from days 1–7 followed by C. difficile inoculum on day 8. Additionally, the animals received Lactobacillus acidophilus (Group III) and EGF (Group IV) for one‐week post C. difficile challenge. The animals were evaluated for colonization and toxin production by C. difficile, myeloperoxidase (MPO) activity and histopathological changes. Results: Clostridium difficile was colonized and elaborated its toxins in animals receiving cyclosporin and C. difficile. MPO activity was significantly higher (P < 0.05) and histopathological epithelial damage, cryptitis and acute inflammatory changes were seen in the cecum and colon. C. difficile count, toxins A and B titers and MPO activity were significantly lowered (P < 0.05) in animals receiving probiotic and EGF. Histopathologically, mucodepletion and inflammatory infiltrate were decreased in the biotherapeutic receiving animals. Conclusions: Cyclosporin led to the development of mild to moderate CDAD in animals. Administration of biotherapeutics reduced the severity of CDAD. Future clinical trials are needed for further investigation of these potential biotherapeutic measures.     

GVHD prophylaxis using low‐dose cyclosporine improves survival in leukaemic recipients of HLA‐identical sibling transplants

Graft‐versus‐host disease (GVHD) prophylaxis of short duration (6 months) with low‐dose cyclosporine A (CsA) starting at 1 mg/kg per day i.v. and four doses of methotrexate (MTX) were given to 171 consecutive leukaemic recipients of HLA‐identical sibling transplants. In contrast, apart from MTX, retrospective controls received high‐dose CsA, starting at 5–7.5 mg/kg per day i.v. and discontinued 1 yr post‐transplant. In the low‐dose CsA group, the probability of acute GVHD grades I–II (70% vs. 53%, P < 0.01), and chronic GVHD were increased (58% vs. 25%, P < 0.01), whereas the incidences of acute GVHD grades III–IV (9% vs. 5%, P = 0.62), and non‐relapse mortality (20% vs. 22%, P = 0.58) were similar. Moreover, the probability of relapse was decreased (31% vs. 54%, P < 0.01), and both relapse‐free (56% vs. 38%, P = 0.04) and overall survival (61% vs. 40%, P = 0.04) were markedly improved using the low‐dose CsA regimen. In multivariate analyses, low‐dose CsA was strongly associated with chronic GVHD [relative hazard (RH) 2.56, P < 0.01], which decreased the risk of relapse (RH 0.46, P < 0.01) and improved the probability of survival (RH 1.84, P < 0.01). In conclusion, a low‐dose CsA regimen in leukaemic recipients of HLA‐identical sibling transplants increases the rate of chronic GVHD, which seems to attenuate the risk of relapse, thereby improving patient survival owing to enhanced graft‐versus‐leukaemia effect.     

Effects of Renin‐Angiotensin‐Aldosterone System Blockade on Chlorhexidine Gluconate‐Induced Sclerosing Encapsulated Peritonitis in Rats

Sclerosing encapsulated peritonitis (SEP) is a rare complication of long term peritoneal dialysis. Renin‐angiotensin‐aldosterone system (RAAS) may play a role in the development of peritoneal fibrosis in CAPD patients. We aimed to evaluate the effect of aliskiren, valsartan, and aliskiren + valsartan therapy on SEP. The study included 30 Wistar albino rats which were divided into five groups: I (Control) SF solution i.p.; II (CG group) chlorhexidine gluconate i.p.; III aliskiren oral plus CG i.p.; IV valsartan oral plus CG i.p.; and V aliskiren oral, valsartan oral and CG i.p. On the twenty‐first day, all of the rats were sacrificed. All of the groups were analyzed in terms of peritoneal thickness, degree of inflammation, vasculopathy, neovascularization and fibrosis. Also, the parietal peritoneal tissue samples were evaluated for matrix metalloproteinase 2 (MMP‐2) using the ELISA method. Peritoneal thickness and fibrosis scores were lower in the valsartan group compared to the CG group (P < 0.05). Peritoneal fibrosis scores were lower in the aliskiren group compared to CG group (P < 0.05) but no difference was observed between the peritoneal thickness scores of the two groups (P > 0.05). Tissue MMP‐2 levels were significantly higher in the CG group compared other groups (P < 0.05). There were no statistically significant differences between the aliskiren, valsartan and aliskiren + valsartan groups according to the tissue MMP‐2 levels. Due to the antifibrotic properties of valsartan, it is thought to be a possible choice to prevent SEP development. We found no positive impact of aliskiren or aliskiren + valsartan combination compared to valsartan alone.     

Post‐transplantation cyclophosphamide versus conventional graft‐versus‐host disease prophylaxis in mismatched unrelated donor haematopoietic cell transplantation

Post‐transplantation cyclophosphamide (PTCy) is an effective strategy to prevent graft‐versus‐host disease (GVHD) after haploidentical haematopoietic cell transplantation (HCT). We determined the efficacy of PTCy‐based GVHD prophylaxis in human leucocyte antigen (HLA)‐mismatched unrelated donor (MMUD) HCT. We analysed 113 adult patients with high‐risk haematological malignancies who underwent one‐antigen MMUD transplantation between 2009 and 2013. Of these, 41 patients received PTCy, tacrolimus and mycophenolate mofetil (MMF) for GVHD prophylaxis; 72 patients received conventional prophylaxis with anti‐thymocyte globulin, tacrolimus and methotrexate. Graft source was primarily bone marrow (83% PTCy vs. 63% conventional group). Incidence of grade II–IV (37% vs. 36%, P = 0·8) and grade III–IV (17% vs. 12%, P = 0·5) acute GVHD was similar at day 100. However, the incidence of grade II‐IV acute GVHD by day 30 was significantly lower in the PTCy group (0% vs. 15%, P = 0·01). Median time to neutrophil (18 days vs. 12 days, P < 0·001) and platelet (25·5 days vs. 18 days, P = 0·05) engraftment was prolonged in PTCy group. Rates of graft failure, chronic GVHD, 2‐year non‐relapse mortality, relapse, progression‐free survival or overall survival were similar. Our results demonstrate that PTCy, tacrolimus and MMF for GVHD prophylaxis is safe and produced similar results as conventional prophylaxis in patients with one antigen HLA‐MMUD HCT.     

Effects of high‐intensity focused ultrasound and anti‐angiogenic agents on the ablation of experimental liver cancers

OBJECTIVE : To assess the efficacy of high‐intensity focused ultrasound (HIFU) when combined with heparin and cortisone acetate in treating experimental liver cancer LTNM₄ implanted subcutaneously in nude mice. METHODS : High‐intensity focused ultrasound treatment was administered with a focused 1.1 MHz transducer at a peak intensity of 750 W/cm² for a continuous exposure of 20 s and, 1 day later, heparin (300 U/mL) was given orally in drinking water and an initial dose of 250 mg/kg cortisone acetate was injected subcutaneously into each mouse. Forty‐eight mice with tumors were randomly divided into four groups. Group I (n = 12) were controls; Group II (n = 12) received heparin and cortisone therapy; Group III (n = 12) received HIFU therapy only; Group IV (n = 12) received both HIFU, heparin and cortisone therapy. RESULTS : Significant inhibition of tumor growth was seen in groups II, III and IV as compared with group I (P < 0.05), with the tumor growth inhibition rate on the 28th day being 86, 90 and 99%, respectively. All mice in group IV were cured, with no evidence of tumors by the 35th day and, histologically, no tumor cells remained. CONCLUSIONS : The data suggest that HIFU can destroy liver cancer effectively and that HIFU combined with treatment using the anti‐angiogenic agents heparin and cortisone may constitute a comprehensive treatment to ablate liver cancer.     

Clinical Effects of Pulse High‐Volume Hemofiltration on Severe Acute Pancreatitis Complicated With Multiple Organ Dysfunction Syndrome

To evaluate the effects of pulse high‐volume hemofiltration (PHVHF) on severe acute pancreatitis (SAP) with multiple organ dysfunction syndrome (MODS). Thirty patients were divided into two groups: PHVHF group and continuous venovenous hemofiltration (CVVH) group. They were evaluated in terms of clinical symptoms, acute physiology and chronic health evaluation (APACHE) II score, sequential organ failure assessment (SOFA) score, simplified acute physiology (SAPS) II score and biochemical changes. The levels of IL‐6, IL‐10 and TNF‐α in plasma were assessed by ELISA before and after treatment. The doses of dopamine used in shock patients were also analyzed. In the two groups, symptoms were markedly improved after treatment. Body temperature (BT), breath rate (BR), heart rate (HR), APACHE II score, SOFA score, SAPS II score, serum amylase, white blood cell count and C‐reactive protein were decreased after hemofiltration (P < 0.05). The PHVHF group was superior to the CVVH group, especially in APACHE II score, CRP (P < 0.01), HR, temperature, SOFA score and SAPS II score (P < 0.05). The doses of dopamine for shock patients were also decreased in the two groups (P < 0.05), with more reduction in the PHVHF group than the CVVH group (P < 0.05). The levels of IL‐6, IL‐10 and TNF‐α decreased (P < 0.05) in the PHVHF group more significantly than the CVVH group (P < 0.01). PHVHF appears to be superior to CVVH in the treatment of SAP with MODS.     

Melatonin: Antioxidant and modulatory properties in age‐related changes during Trypanosoma cruzi infection

The purpose of this study was to investigate the effects of melatonin on selected biomarkers of innate and humoral immune response as well as the antioxidant/oxidant status (superoxide dismutase—SOD and reduced glutathione levels (GSH) to understand whether age‐related changes would influence the development of acute Trypanosoma cruzi (T. cruzi) infection. Young‐ (5 weeks) and middle‐aged (18 months) Wistar rats were orally treated with melatonin (gavage) (05 mg/kg/day), 9 days after infection. A significant increase in both SOD activity and GSH levels was found in plasma from all middle‐aged melatonin‐treated animals. Melatonin triggered enhanced expression of major histocompatibility class II (MHC‐II) antigens on antigen‐presenting cell (APC) and peritoneal macrophages in all treated animals. High levels of CD4⁺CD28‐negative T cells (*P<.05) were detected in middle‐aged control animals. Melatonin induced a significant reduction (***P<.001) in CD28‐negative in CD4⁺ and CD8⁺ T cells in middle‐aged control animals. Contrarily, the same group displayed upregulated CD4⁺CD28⁺T and CD8⁺CD28⁺T cells. Melatonin also triggered an upregulation of CD80 and CD86 expression in all young‐treated groups. Significant percentages of B and spleen dendritic cells in middle‐aged infected and treated animals were observed. Our data reveal new features of melatonin action in inhibiting membrane lipid peroxidation, through the reduction in 8‐isoprostane, upregulating the antioxidant defenses and triggering an effective balance in the antioxidant/oxidant status during acute infection. The ability of melatonin to counteract the immune alterations induced by aging added further support to its use as a potential therapeutic target not only for T. cruzi infection but also for other immunocompromised states.     

Phase II trial of ofatumumab plus ESHAP (O‐ESHAP) as salvage treatment for patients with relapsed or refractory classical Hodgkin lymphoma after first‐line chemotherapy

The management of recurrent/refractory (R/R) Hodgkin lymphoma (HL) remains challenging. Previously published data have shown some efficacy of rituximab in this setting. The purpose of this phase II trial was to investigate the activity of ofatumumab in combination with etoposide, steroids, cytarabine and cisplatin (O‐ESHAP) in 62 patients with R/R classical HL. Treatment consisted of ESHAP plus ofatumumab 1000 mg on days 1 and 8 of the first cycle and day 1 of the second and third cycles. O‐ESHAP was well tolerated with only 3% of patients requiring treatment discontinuation because of adverse events. Overall response rate was 73% (44% complete metabolic response). In multivariate analysis, early relapse (P < 0·001), bulky disease (P < 0·001) and B symptoms (P < 0·001) were the most important prognostic factors for response. No failures of stem cell mobilization were observed. The high response rate, particularly the complete metabolic response rate, the low toxicity profile, and the high mobilizing potential of the O‐ESHAP regimen suggest that patients with R/R HL may benefit from this salvage regimen. However, with the encouraging results observed with other new therapeutic agents in HL, the O‐ESHAP regimen could be restricted to patients failing these agents or to those with R/R nodular lymphocyte‐predominant HL.     

Arterial duct stenting in low‐weight newborns with duct‐dependent pulmonary circulation

Objectives: To evaluate feasibility and results of arterial duct (AD) stenting in low‐weight newborns with congenital heart disease and duct‐dependent pulmonary circulation (CHD‐DPC). Background: AD stenting is nowadays considered a cost‐effective alternative to surgical shunt in CHD‐DPC. This option might be even more advisable in low‐weight neonates (<2.5 kg), who are at higher surgical risk and in whom stent redilation might adapt shunt magnitude to patient's growth. Methods: Between April 2003 and September 2010, 76 neonates with CHD‐DPC underwent AD stenting at our institution, as lower‐risk palliation with respect to surgical shunt. Procedural and follow‐up data of the 15 low‐weight newborns (2.0 ± 0.3 kg, median 2.2) (group I) were compared with the remaining normal‐weight newborns (3.5 ± 0.7 kg, median 3.2) (group II). Results: Feasibility, complication rate, and need for surgical shunt did not significantly differ between groups. Global X‐ray exposure was significantly higher in the low‐weight group (82 ± 108 vs. 30 ± 33 Gray/cm², P < 0.002), which maybe due to a longer angiographic presenting work‐up. In‐hospital mortality rate was 14.3% (vs. 1.9% in the group II, P = NS), although none of the fatalities was procedure‐related. During follow‐up, five patients (35.7% vs. 15.7% in the group II, P = NS) underwent stent redilation before surgical repair. At control angiography, the Nakata and McGoon indexes had significantly increased (P < 0.05 for both comparisons), without any significant difference with the group II (162 ± 52% vs. 144 ± 158% and 40 ± 17% vs. 42 ± 38%, P = NS). Conclusions: AD stenting is also feasible and effective in low‐weight newborns with CHD‐DPC, supporting the spontaneous improvement process or promoting a significant pulmonary artery growth. © 2011 Wiley‐Liss, Inc.     

Urokinase‐type plasminogen activator system and human cationic antimicrobial protein 18 in serum and induced sputum of patients with chronic obstructive pulmonary disease

Background and objective: There is increasing evidence that the innate immune system plays an important role in the pathogenesis of COPD. The objective of this study was to quantify several innate immune biomarkers in serum and induced sputum of COPD patients, and healthy non‐smokers and smokers. Methods: Serum and induced sputum levels of urokinase‐type plasminogen activator (uPA), urokinase‐type plasminogen activator receptor (uPAR), urokinase‐type plasminogen activator inhibitor (PAI‐1) and human cationic antimicrobial protein 18 (CAP18) were measured by ELISA, in 13 patients with stage I or stage II COPD (COPD I + II), 15 patients with stage III or stage IV COPD (COPD III + IV), 18 healthy non‐smokers and 14 healthy smokers. In addition, membrane‐bound uPAR in peripheral blood and induced sputum was assessed by flow cytometry. Results: Levels of uPAR, PAI‐1 and CAP18 were elevated in induced sputum of COPD I + II and COPD III + IV patients, compared with healthy non‐smokers (P < 0.05) and healthy smokers (P < 0.05). uPAR, PAI‐1 and CAP18 levels were significantly higher in COPD III + IV patients compared with COPD I + II patients (P < 0.05). The expression of uPAR on induced sputum neutrophils and macrophages was significantly higher in COPD patients compared with healthy non‐smokers (P < 0.05) and healthy smokers (P < 0.05). Sputum uPAR and CAP18 levels showed significant inverse correlations with FEV₁% and 6MWD, and significant positive correlations with St. George's Respiratory Questionnaire scores. Conclusions: In COPD patients, increased induced sputum levels of uPAR, PAI‐1 and CAP18 were associated with airflow limitation, health status and exercise tolerance, suggesting that these biomarkers may be implicated in the pathogenesis of COPD.     

Clinical significance of half‐lives of tumor markers α‐fetoprotein and des‐γ‐carboxy prothrombin after hepatectomy for hepatocellular carcinoma

Aim

The prognostic significance of the half‐lives (HLs) of α‐fetoprotein (AFP) and des‐γ‐carboxy prothrombin (DCP) in patients undergoing hepatectomy for hepatocellular carcinoma (HCC) is unclear. We evaluated the HLs of AFP and DCP in a cohort of such patients.

Methods

This study included data on 202 patients with HCC who underwent curative hepatectomy and had preoperative AFP concentrations ≥100 ng/mL or DCP ≥200 mAU/mL. We calculated the HLs of AFP and DCP from their values just before and 1 month after hepatectomy. We identified three groups: a normalization group, tumor marker concentrations within normal range 1 month post‐hepatectomy; a long group, HL of AFP ≥7 days or DCP ≥4 days; and a short group, remaining patients. We evaluated associations between HL and prognosis.

Results

Three‐year recurrence‐free survival (RFS) in the normalization (n = 70), short (n = 71), and long groups (n = 61) was 41.3%, 46.0%, and 16.8%, respectively (P = 0.002). Five‐year overall survival (OS) of normalization, short, and long groups was 72.6, 70.6 and 43.8%, respectively (P = 0.002). Multivariate analysis revealed that long HL is an independent risk factor for poor RFS (hazard ratio [HR] 2.21, P = 0.0006) and poor OS (HR 2.70, P = 0.004). The extrahepatic recurrence rate was 21.3% (13/61) in the long group, which is higher than in the normalization group (8.6%, 6/70) (P = 0.04) and short group (9.9%, 7/71) (P = 0.07).

Conclusion

Post‐hepatectomy HLs of AFP and DCP are predictors of long‐term outcome in patients with HCC.     

Hyperbaric oxygen-induced changes in bacterial translocation and acinar ultrastructure in rat acute necrotizing pancreatitis

Background We aimed to investigate the effects of hyperbaric oxygen therapy on bacterial translocation and acinar cell ultrastructure in a rat model of acute necrotizing pancreatitis. Methods Forty-eight male Sprague-Dawley rats were randomly divided into three groups. Acute pancreatitis was induced in groups II and III. Groups I and II did not receive any treatment, and group III was treated with hyperbaric oxygen. All surviving animals were killed 48 h after the induction of pancreatitis. Bacterial translocation and histological and ultrastructural changes were determined. Results The incidence of bacterial translocation in group III was significantly lower in comparison with group II (P < 0.001). Histopathological and ultrastructural injury scores were also significantly lower in group III (P < 0.001 and P < 0.04, respectively). Conclusions Hyperbaric oxygen therapy displayed beneficial effects on pancreatic superinfection and or histopathological and ultrastructural changes in experimental necrotizing pancreatitis.